1. Field of the Invention
This invention relates to aerosol drug formulations. This invention also relates to methods of preparing aerosol drug formulations and to methods of filling aerosol canisters.
2. Description of the Related Art
Conventional chlorofluorocarbon based medicinal aerosol formulations generally contain a relatively nonvolatile component (e.g., trichlorofluoromethane, propellant 11), a surfactant, a drug, and a volatile propellant system (e.g., a combination of dichlorodifluoromethane, propellant 12, and dichlorotetrafluoroethane, propellant 114). Such formulations can be filled into individual aerosol canisters by one of two conventional methods: pressure filling or cold filling. Cold filling generally involves the preparation of a mixture of the nonvolatile components at room temperature and ambient pressure to form a concentrate. This concentrate is then cooled to a temperature at which the remaining components are liquid at ambient pressure. The volatile components are also cooled and added to the concentrate to afford a liquid formulation that is filled into individual canisters, also at reduced temperature. A valve is crimped into place on the canister and the finished product is allowed to warm to ambient temperature.
Pressure filling involves the same preparation of a concentrate of the nonvolatile components. An appropriate amount of the concentrate is metered into an individual canister at ambient temperature and pressure. A valve is then crimped into place. The volatile components are then added to the canister via the valve under pressure sufficient to liquify the volatile components.
European Patent Application 0,419,261 (Burt et al.) describes a method of introducing into a container a suspension or solution of a material in a propellant held under pressure. The method comprises bringing a filling head into communication with a container, introducing a quantity of the suspension or solution into the container through the filling head, introducing a quantity of a high pressure propellant into the filling head while it is still in communication with the container, thereby flushing through any suspension or solution remaining in the filling head. This pressure filling method is said to avoid the escape of pharmaceutical material when the filling head is removed from the container.